Drawing Out the Facts

The STEM Chicksmas Day Eleven: Telomerase

For the 12 Days of “The STEM Chicksmas” we’re highlighting 12 scientists who have contributed something innovative and exciting to their field. It is the season of giving, and these brilliant minds have given incredible gifts to the scientific community! This year we’re looking at 12 Nobel Prize winners from the past 15 years in the fields of Physics, Chemistry, and Physiology or Medicine.

In cell mitosis, the process by which a cell divides, the parent cell yields two genetically identical daughter cells, meaning they have identical DNA. But how? Why aren’t the chromosomes, which are packaged up DNA strands, degraded and shortened? It turns out that they are—but not quite in the way we would expect. The discovery of the roles of telomeres and telomerase by Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak won the 2009 Nobel Prize in Medicine.

The problem with chromosomes shortening comes down to the way DNA is copied. During mitosis, the double-stranded DNA is separated into a leading strand and a lagging strand. The leading strand is copied (for simplicity, we say “copied,” but the process actually copies the complement, more accurately termed replication) all at once, whereas the lagging strand has to be copied in short segments by an enzyme called DNA polymerase. However, the polymerase cannot just start copying the DNA. Instead, it needs a single-stranded primer made out of RNA to bind to the lagging template DNA. The polymerase can then copy the fragments, and the gaps in between the fragments are later filled in when the RNA primer is removed. However, the gap caused by the RNA primer at the end of the strand cannot be filled in, meaning that there is always a gap at the end of the copied chromosome. Despite this gap our DNA seems to be being copied correctly.

In the early 1900s cell biologists hypothesized that telomeres might play a protective role, because they observed that they prevented chromosomes from bonding together. Telomeres are the bits at the end of the chromosome, and in the 1970s Blackburn discovered that they contain a genetic sequence that repeats over and over again, 20-70 times, differing between chromosomes. Why were they different lengths?

More confusion arose when Blackburn and Szostak were working on yeast cells, trying to see what happened with these telomeres. They found that when DNA was replicated, it was not only truncated but could also grow longer. This was a confusing conclusion, because it went against the way DNA replication was understood at that time. Furthermore, the part that was added onto the sequence didn’t seem to come from a replication of original template DNA, but rather from an extension of the parent strand. A breakthrough came when Blackburn’s graduate student, Greider, designed a clever experiment. She made an extract of a certain type of cell, Tetrahymena, and mixed it with radioactively tagged nucleotides (building blocks of DNA) and artificial telomere DNA. The radioactively tagged nucleotides ended up being assembled in the same sequenceas those naturally occurring in Tetrahymenda. This led to the discovery of the enzyme telomerase. Telomerase adds telomeres onto the end of chromosomal strands based on its biological own sequence. This is why telomerase in the cell extract added the same telomeric sequence characteristic of Tetrahymenda to the ends of the artificial telomeres, using the radioactively tagged nucleotides. This prevents the problem of the gap that occurs when replicating DNA by lengthening the chromosome before replication!

The discovery of telomerase has given a lot of insight into how DNA replicates. Since then, researchers have found that cells in older organisms have chromosomes with truncated telomeres. It is possible that the telomere length and aging are related. Furthermore, because telomerase allows multiple divisions of a cell, high telomerase activity can allow unlimited division, leading to cancer. This would have never been recognized without the discovery of telomerase. We can now better investigate the cause of diseases, especially congenital diseases, expanding our knowledge and possibly leading to a cure.

To read more, check out the Nobel Prize website or the award winning work here.